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Nanovaccines have attracted booming interests in vaccinology studies, but the profound impacts of their delivery mode on immune response remain unrealized. Herein, immunostimulatory CpG‐modified tumor‐derived nanovesicles (CNVs) are used as a nanovaccine testbed to initially evaluate the impacts of three distinct delivery modes, including mono‐pulse CNVs, staggered‐pulse CNVs, and gel‐confined CNVs. Fundamentally, delivery mode has enormous impacts on the immunomodulatory effects, altering the spatiotemporal distribution of nanovaccine residence and dendritic cell–T cell interaction in lymph nodes, and finally affecting subsequent T cell‐mediated immune performance. As a result, the gel‐confined delivery mode offers the best therapeutic performance in multiple tumor models. When extending evaluation to examine how the various delivery modes impact the performance of liposome‐based nanovaccines, similar trends in intralymph node distribution and antitumor effect are observed. This work provides a strong empirical foundation that nanovaccine researchers should position delivery mode near the top of their considerations for the experimental design, which should speed up nanovaccine development and facilitate efficient selection of appropriate delivery modes in the clinic. [ABSTRACT FROM AUTHOR]

Background: Tenofovir disoproxil fumarate (TDF) imposes a high genetic barrier to drug resistance and potently inhibits replication of multidrug‐resistant hepatitis B virus. Few clinical cases with confirmed TDF‐resistance have been reported to date. Methods and Results: Here, we report viral rebound in a patient with chronic hepatitis B who underwent TDF monotherapy and harboured a quadruple mutant consisting of classic entecavir (ETV)‐resistance mutations (rtL180M/T184L/M204V) together with an rtA200V mutation in the reverse transcriptase gene. Sequencing analysis revealed that this quadruple mutant emerged as a major viral population. In vitro phenotyping demonstrated that the rtL180M/T184L/A200V/M204V mutant had moderate resistance to TDF treatment, with a 4.52‐fold higher half maximal effective concentration than that of wild‐type virus. Importantly, this patient with TDF resistance achieved virological suppression after TDF/ETV combination rescue therapy. Conclusion: An rtL180M/T184L/A200V/M204V mutant with moderate resistance to TDF monotherapy was selected during sequential nucleoside analogue (NA) treatment in a stepwise manner. ETV/TDF combination therapy effectively suppressed replication of this TDF‐resistant mutant. Our studies provide novel insights into the treatment of NA‐naïve patients as well as patients with TDF resistance. [ABSTRACT FROM AUTHOR]

Background and Aim: Results obtained from different hepatitis E virus (HEV) tests are usually inconsistent. The detection of serum HEV antigen (Ag) has been suggested to be more sensitive for the diagnosis of genotypes 1 and 3 HEV. Methods: We compared the diagnostic accuracies of serum HEV Ag and HEV RNA by using 202 serum samples from patients suspected acute viral hepatitis. Results: The HEV Ag assay was 100% specific. The lower detected levels of viremia ranged from 102 to 103 copies/mL. The sensitivity of the HEV Ag test was 90.5%. One of the 42 cases was negative for anti‐HEV IgM, but HEV Ag was still detectable. The detectable period of HEV Ag was in concordance with the detectable period of HEV RNA. Serum HEV Ag was persistently detected in two cases of chronic hepatitis E, confirmed by the persistent presence of HEV RNA despite being negative for anti‐HEV IgM. HEV Ag demonstrated good consistency with positive HEV RNA (k = 0.938, P < 0.001). Receiver operating characteristic analysis of HEV Ag suggested a second cut‐off value of >0.095 to predict HEV patients with 95.24% sensitivity and 98.75% specificity, and the area under the curve was 0.9887, which was higher than that of three commercial anti‐HEV IgM ELISA tests. Conclusions: The presence of HEV Ag has good consistency with HEV RNA in both acute and chronic genotype 4 hepatitis E. HEV Ag is a more promising serum marker to identify active genotype 4 HEV infection than anti‐HEV IgM and HEV RNA. [ABSTRACT FROM AUTHOR]

The cover image is based on the Original Article I Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance i by Xianbo Wang, Jianghua Wang, Dong Jiang et al., https://doi.org/10.1111/liv.14241 GLO:Q18/01jan20:liv14317-toc-0001.jpg PHOTO (COLOR): . gl. [Extracted from the article]

Objective To examine associations between metabolic syndrome (MetS) and its individual components with risk of mild cognitive impairment ( MCI) among community elderly and explore the age difference. Design Cross-sectional study. Subjects About 2 102 aged 60 and older community residents in Beijing metropolitan area, China. Measurements Cognitive function was assessed by Mini-Mental State Examination ( MMSE). MetS was defined by the 2009 harmonizing definition. Overnight-fasting blood samples were obtained to measure biochemistry indicators. Results The prevalence of MetS and MCI was 59·1% and 15·9%, respectively. After adjusting age, gender, other demographic factors, lifestyle variables and medication use, participants with MetS or its individual components are at significantly elevated risk for MCI. In terms of MMSE score, as the continuous dependent variable, the β (95% CI) of MetS was −0·68(−0·99, −0·37). For prevalence of MCI, as the dichotomy dependent variable, the odds ratio ( OR) of Mets is 1·52 compared to control group (or baseline) with 95% confidence interval ( CI) of 1·16 to 1·95. The multivariate association only showed significant results among participants aged less than 80 years old. Conclusions MetS is associated with worse cognitive function among younger elderly. Managing MetS, as well as its components, may contribute to control cognitive decline and reduce related disease and social burden. [ABSTRACT FROM AUTHOR]